M. V. Ramana

Investigation of Enhancement of Solubility of Norfloxacin β-Cyclodextrin in Presence of Acidic Solubilizing Additives

The present study is aimed at improving the solubility of a poorly water-soluble drug, norfloxacin by incorporating solubilizing additives such as ascorbic acid and citric acid into the beta-cyclodextrin complexes. Norfloxacin, being amphoteric in nature, exhibits a higher solubility at pH below 4 and above 8. Addition of substances like ascorbic acid and citric acid in beta-cyclodextrin complexes reduces the pH of the immediate microenvironment of the drug below pH 4. In the present work, beta-cyclodextrin complexes of norfloxacin were prepared along with solubilizing additives such as citric acid and ascorbic acid in various proportion and the dissolution profile was performed in both HCl buffer, pH 1.2 and phosphate buffer, pH 7.4. The results have shown an enhanced dissolution rate in both media. DSC and IR spectral studies performed on the solid complexes have shown that there is no interaction of the drug with the additives and beta-cyclodextrin. Disc diffusion studies have shown larger diameters of zone of inhibition indicating a greater diffusivity of the drug into the agar medium.

Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac.

The objective of the present investigation was to study the effect of β-cyclodextrin (β-CD) on the in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. Aceclofenac molecular inclusion complexes in 1:1 and 1:2 M ratio were prepared using a kneading method. The in vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes was carried out. Molecular inclusion complexes of AF with β-CD showed a considerable increase in the dissolution rate in comparison with the physical mixture and pure drug in 0.1 N HCl, pH 1.2, and phosphate buffer, pH 7.4. Inclusion complexes with a 1:2 M ratio showed the maximum dissolution rate in comparison to other ratios. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD in complexes in solid state. Molecular modeling results indicated the relative energetic stability of the β-CD dimer-AF complex as compared to β-CD monomer-AF. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with β-CD. The in vitro release from all the formulations was best described by first-order kinetics (R2 = 0.9826 and 0.9938 in 0.1 N HCl and phosphate buffer, respectively) followed by the Higuchi release model (R2 = 0.9542 and 0.9686 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, the dissolution of AF can be enhanced by the use of a hydrophilic carrier like β-CD.

Aceclofenac topical dosage forms: in vitro and in vivo characterization.

Aceclofenac topical dosage forms: In vitro and in vivo characterization Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1% (m/m) aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations. Dozirani pripravci aceklofenaka za topičku primjenu: In vitro i in vivo karakterizacija Aceklofenak je lijek nove generacije nesteroidnih protuupalnih lijekova sa izraženim protuupalnim i analgetskim djelovanjem. Dostupan je u obliku tableta od 100 mg. U ovom radu razvijeni su dozirani pripravci za topičku primjenu u svrhu smanjenja ili uklanjanja nuspojava povezanih s oralnom primjenom nesteroidnih protuupalnih lijekova. Ti pripravci mogu se upotrijebiti kao dodatak peroralnoj terapiji artritisa i srodnih bolesti. Opisana je priprava mazila, krema i gela s 1% m/m aceklofenaka te njihova fizička svojstva, pH, mazivost, istiskivost, jednolikost sadržaja ljekovite tvari, difuzija i permeabilnost in vitro. Nakon analize rezultata za daljnja ispitivanja odabrani su gelovi pripravljeni na bazi Carbopola 940 (AF2, AF3) i makrogola (AF7). Ispitana je akutna iritacija kože, protuupalno i analgetsko djelovanje koristeći karagenom induciranu termičku hiperalgeziju i edem šape. Pripravak AF2 bio je značajno (p < 0,05) učinkovitiji u inhibiciji hiperalgezije s upalom nego pripravci AF3 i AF7. Stoga se AF2 može predložiti kao alternativa peroralnim pripravcima.

An approach to minimize Pseudomembranous colitis caused by clindamycin through liposomal formulation

Liposomal encapsulation is known to significantly improve the therapeutic index of a drug. In the present investigation liposomal formulations were chosen to transport clindamycin, which is considered as the most effective topical antibiotic for acne, into the skin layers. Liposomes with clindamycin phosphate were prepared using lipid film hydration method and the optimum ratio of the components was determined. The liposomes were characterized for their vesicle size, shape, encapsulation efficiency, % drug content and for in vitro skin permeation study. The results suggest that the average size of vesicles was found to be in range of 4.91-6.75 µm. Highest encapsulation efficiency (45.4%) and in vitro skin permeation (62%) was achieved with a formulation containing drug: lipid: cholesterol in the ratio of 1:1:1. Liposomal formulation of clindamycin phosphate with good skin permeation properties was incorporated into gel base and comparison of in vitro skin permeation was made with non liposomal marketed gel, both containing 1% clindamycin phosphate. Higher rate of drug release across the rat abdominal skin was found with liposomal gel (54%) than non-liposomal marketed gel (48.7%). Biological study revealed that by encapsulating clindamycin phosphate into liposomes the occurrence of Pseudomembranous colitis could be reduced significantly in comparison to plain clindamycin phosphate.

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.

High-performance thin-layer chromatographic analysis for the simultaneous quantification of gallic acid, vanillic acid, protocatechuic acid, and quercetin in the methanolic fraction of Limonia acidissima L. fruits

A high-performance thin-layer chromatography (HPTLC) method for the simultaneous quantitative determination of gallic acid, vanillic acid, protocatechuic acid, and quercetin in methanolic fractions of Limonia acidissima L. fruits was developed for the first time for this species. Methanol was found to be the best for the highest possible recovery of the target analytes. For achieving good separation, a mobile phase of toluene—ethyl acetate—formic acid (5:4:1 v/v) was used. The densitometric determination was carried out at 310 and 254 nm in reflection—absorption mode. The calibration curves were linear in the range of 100–600 ng per spot for gallic acid, vanillic acid, protocatechuic acid, and quercetin. The methanolic fractions of L. acidissima L. fruits showed the presence of gallic acid (0.07%), vanillic acid (0.16%), protocatechuic acid (0.06%), and quercetin (0.14%). The proposed method is simple, precise, speciffic, and accurate. The statistical analysis of the data obtained proves that the method is reproducible and selective and can be used for the routine analysis of the reported phenolic compounds in crude drug and extracts. The simultaneous quantification of these compounds has not been reported yet in L. acidissima L., which may be utilized for the proper standardization of the drug.

Enhancement of Dissolution Behavior of Aceclofenac by Complexation with β-Cyclodextrin-Choline Dichloride Coprecipitate

The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. The molecular inclusion complexes of AF with β-CD coprecipitated with CDC in 1:1 and 1:2 M ratio were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes (AF-β-CD-CDC) were carried out. Molecular inclusion complexes of aceclofenac with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH, 7.4. Inclusion complexes with 1:2 M ratio showed maximum dissolution rate in comparison to other ratios. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics (R 2 = 0.9354 and 0.9268 in 0.1 N HCl and phosphate buffer, respectively) followed by Higuchi release model (R 2 = 0.9029 and 0.9578 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, dissolution of aceclofenac can be enhanced by using the β-CD-CDC coprecipitate as a host molecule.

Preparation and Characterization of Solid Dispersions of Rofecoxib

The present study is aimed at improving the dissolution of poorly soluble drug, rofecoxib, using solid dispersion technique. The solid dispersions were prepared in different proportions using hydrophilic carriers like mannitol, and urea. The dissolution rate studies were performed in both simulated gastric fluid and simulated intestinal fluid. It is observed that the dissolution was affected by the acidity of the medium. Solid dispersions gave faster dissolution rate when compared to corresponding physical mixture and pure drug. In vivo absorption and anti-inflammatory activity studies of solid dispersions also confirmed the above results. The DSC thermogram and IR spectra revealed that there is no interaction of Rofecoxib with additives and the drug, rofecoxib is stable in solid dispersions.

Gas chromatography–mass spectrometry and high-performance thin-layer chromatography quantifications of some physiologically active secondary metabolites in Averrhoa carambola L. fruits

The extraction of crude drugs by using different solvents provides polarity-based fractions containing specific types of secondary metabolites. Averrhoa carambola L. fruits were extracted and fractionated, and petroleum ether extract was processed by fatty acid methyl ester (FAME) technique for characterization by gas chromatography–mass spectrometry (GC–MS) analysis. The remaining part was extracted with methanol for high-performance thin-layer chromatography (HPTLC) analysis, for simultaneous quantitative determination of gallic acid, protocatechuic acid, and quercetin in methanolic fractions. Petroleum ether and methanol fractions were found to be the best for the highest possible recovery of target analytes. The chromatographic elutions of FAME compounds generated from ether extract were evaluated by GC–MS profiling. Ten fatty acid compounds were separated with the highest quantity of oleic acid methyl ester (42.88%). On other hand, polar fraction was processed by HPTLC profiling. For achieving good separation, a mobile phase of toluene–ethyl acetate–formic acid (5:4:1, v/v) was used. The densitometric determination was carried out at 310 nm in reflection–absorption mode. The calibration curves were linear in the range of 100–600 ng per spot for gallic acid, protocatechuic acid, and quercetin. During the analysis, the dried raw material from A. carambola L. fruits showed the presence of gallic acid (0.96%), protocatechuic acid (0.05%), and quercetin (0.40%). The proposed method is simple, precise, specific, and accurate. The statistical analysis of the data obtained proves that the method is reproducible and selective and can be used for the routine analysis of the reported phenolic compounds in crude drug and extracts. The results indicated that the methanolic extracts of the plant contained a considerable amount of bioactive compounds. The presence of phytochemicals especially phenolics and flavonoids explains its use in various diseases. It may be concluded that the results obtained from the quantitative evaluation of quercetin by HPTLC fingerprinting could be useful in its authentication, the quality control of the drug, and in ensuring therapeutic efficacy.

Preparation, Characterization, and In Vitro Evaluation of Aceclofenac PVP-Solid Dispersions

The objective of the present investigation was to study the effect of polyvinylpyrrolidone (PVP) on in vitro dissolution of aceclofenac from solid dispersions. Aceclofenac binary solid dispersions (SD) with different drug loadings were prepared using the melting or fusion method. In vitro dissolution of pure drug, physical mixtures, and solid dispersions were carried out. Solid dispersion of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH 7.4. Solid dispersions in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. The amorphous nature of the drug in solid dispersion was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in solid dispersion compared to the pure drug. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in solid dispersions in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation, and solubilizing effect of the carrier from the solid dispersions of aceclofenac. In conclusion, dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP.